Modulation of pro-inflammatory mediators by IL-10 in mouse J774 macrophages stimulated with rMOMP-498 of Chlamydia trachomatis (37.5)

Abstract

Abstract We have recently constructed several recombinant major outer membrane proteins (rMOMP) of Chlamydia trachomatis, as potential vaccine candidates. In vitro characterization of the rMOMP-498 (gene fragment corresponding to amino acids 187-344) revealed that it stimulated the production of IL-6, IL-12p40, IL-1β, TNF-α and IL-10 in mouse J774 macrophages. Since IL-10 is a modulator of macrophage activities, we hypothesized that IL-10 induced by rMOMP-498 in macrophages may serve to control inflammation during the initial phase of a C. trachomatis infection. To address our hypothesis we added exogenous mouse IL-10 to J774 cells stimulated with rMOMP-498. IL-10 decreased the production of IL-6, IL12p40 and TNF-α in these cells. Removal of endogenous IL-10 with neutralizing anti-IL-10 Ab in cultures stimulated with rMOMP-498 in part increased the levels of inflammatory mediators as compared to the control Ab. Analyses of CD80, TLR2, TLR4, and CD86 receptors on cells stimulated with rMOMP-498 alone or combined with IL-10 showed no differences in receptor expression levels between the stimulants, suggesting that these receptors are not involved in the IL-10 down-regulatory activities in rMOMP-498-stimulated macrophages. Overall, our data show that IL-10 may be important in the innate immune response to rMOMP-498 as a vaccine candidate. Current studies are underway to identify the mechanism of IL-10 control of the inflammatory response in macrophages.